Successful liver transplantation can be performed across major histocompatibility complex disparities, and studies have shown that immunosuppression can be completely withdrawn in some liver allograft recipients without adverse effects. Regeneration of adult liver is sufficiently robust to permit successful transplantation of reduced size liver grafts. Interestingly, the incidence of rejection and dose of maintenance immunosuppression may be diminished in recipients of partial liver transplants compared to standard whole liver allografts. Defining the mechanisms which create such a privileged immunological environment is relevant to clinical transplantation. Using rat orthotopic whole and partial (50%) liver transplantation models, mechanisms in which recipient MHC-I positive hepatocytes appear in liver allografts after transplantation will be identified, the role of Kupffer cells in repopulation of liver allografts will be determined, and the influence of immunosuppression in the repopulation of liver allografts will be elucidated. Insights into the mechanisms which promote tolerance and regeneration after liver transplantation will provide the basis for the development of novel therapies for the management of allogeneic liver transplant patients.